Hi, thought I'd float this out for comments and ideas.
If one uses subdomain multi-site setup I don't think this is and issue as you can CNAME a subdomain to the multi-site.
But is you use directory structure the you can't use CNAME without causing issues to e-mail as if you CNAME the @ record you force all the DNS records, including MX to the CNAME. So hence, correctly, domain mapping say map the A record (for @ & www) to the server IP address.
But my concern is that by 'hardcoding' the IP address of the server into hundreds or thousands of disparate DNS records is storing up trouble. What happens when you decide to move servers to another providers - you's have to asked you thousands of sites to change IP addresses!
I'm thinking that this implies, don't use directory structure is you are expecting sites you don't (directly) manage to link their domain to you.